本論文主要分成兩個部分：第一部份報導還原去氰反應在有機合成上的應用，其再分成四小節。第一節探討利用雙取代的芳基乙腈化合物11、41與萘化鋰試劑和各類的親電子基試劑進行還原烷化/加成反應，可成功地製備出一般方法不易製備的含有三級取代基之碳環16及雜環77芳香族化合物；第二節探討利用雙取代的丙二腈 84作為起始物可以經由還原烷化/加成反應製備出三取代乙腈94。另外經還原加成與還原消去反應則可製備具有多取代的烯烴類154；第三節探討經由還原加成反應與還原消去反應來建立環外雙鍵雙取代之exo-Glycal；雖然無法成功地合成環外雙鍵雙取代之exo-Glycal，但可成功地將一多取代的乙腈引入醣類中且其具有單一的立體選擇性173；第四節探討經由還原加成反應與還原消去反應來建立丙二烯化合物。
第二部分報導可抗糖尿病的化合物 4-羥基-2-呋喃酸 L-825,373 與其類似物之合成研究。利用indole diglycolate 228與indole glyoxylate 232進行 double Claisen-type縮合反應可一次建立包含中心呋喃環與兩個吲哚環的三個主結構234、235；此亦為本合成研究之關鍵步驟。當indole glyoxylate 244上的2號位置有支鏈存在時，則無法得到縮合產物，而indole diglycolate 241上7號位置的支鏈並不會影響反應的進行。此研究計畫目前仍在進行中。

This thesis consists of two chapters, the first of which is further divided into four sections. The first section deals with the use of lithium naphthalenide and other electron transfer reagents in the reductive alkylation and reductive addition of doubly substituted aryl- and heteroarylacetonitriles such as 11 and 41. Using this process, structural motifs whereby a fully substituted methylene carbon adjacent to an aryl (i.e. 16) or heteroaryl ring (i.e. 77) can be readily generated with high yield. These motifs are difficult to achieve with previously described procedures and protocols. The second section details the results of an investigation into the use of disubstituted malononitrile derivatives as substrates for the reductive alkylation/addition reaction as mediated by lithium naphthalenide. In this way, a route towards the high yielding and easy generation of compounds containing a quarternized carbon is achieved (i.e. 84 --> 94). Additionally, by judicious choice of reacting partner (i.e. cyclohexanone), reductive addition across the carbonyl can be followed by an intramolecular reductive elimination reaction to facilitate the formation fully substituted olefins (i.e. 84 --> 154). The third section reports on the use of the reductive addition reaction to allow for the installation of fully substituted acetonitrile derivatives onto the anomeric carbon of carbohydrates with complete stereoselectivity (i.e. 173). The last section of the first chapter in this thesis recounts the results of the use reductive addition and elimination reactions in the establishment of the structural motif.
The second chapter delineates the work in establishing a total synthesis route to the antidiabetic natural product L-825,373 and its derivatives. The key step of the envisioned synthetic pathway is a double Claisen-type condensation reaction to form the central furan ring. Indole diglycolate 228 and indole glyoxylate 232 were employed as model substrates to test this reaction, giving rise to furanols 234 and 235. In this way, the central pharmacophore of the natural product consisting of a furan and 2 indole rings was established in 1 step. During the course of this research, it was also established that whereas the condensation reaction was not adversely affected by substitution on the C-7 position of indole diglycolate (i.e. 241), it was highly sensitive to substitution on the C-2 position of indole glyoxylate (i.e. 244). The results of this ongoing total synthesis investigation and the methodological investigations detailed above constitutes this thesis.

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72. 節錄自糖尿病關懷協會